Role of the Ubiquitin Proteasome System in Regulating Skin Pigmentation

Hideya Ando,Vincent J Hearing,Masamitsu Ichihashi

doi:10.3390/ijms10104428

Abstract

Pigmentation of the skin, hair and eyes is regulated by tyrosinase, the critical rate-limiting enzyme in melanin synthesis by melanocytes. Tyrosinase is degraded endogenously, at least in part, by the ubiquitin proteasome system (UPS). Several types of inherited hypopigmentary diseases, such as oculocutaneous albinism and Hermansky-Pudlak syndrome, involve the aberrant processing and/or trafficking of tyrosinase and its subsequent degradation which can occur due to the quality-control machinery. Studies on carbohydrate modifications have revealed that tyrosinase in the endoplasmic reticulum (ER) is proteolyzed via ER-associated protein degradation and that tyrosinase degradation can also occur following its complete maturation in the Golgi. Among intrinsic factors that regulate the UPS, fatty acids have been shown to modulate tyrosinase degradation in contrasting manners through increased or decreased amounts of ubiquitinated tyrosinase that leads to its accelerated or decelerated degradation by proteasomes.

Highlights

Solar ultraviolet (UV)-B radiation (290–320 nm) is absorbed by DNA in the epidermis while UV-A radiation (320–400 nm) generates reactive oxygen species in the dermis
Melanin synthesis in the skin, hair and eyes is regulated by tyrosinase, the critical ratelimiting enzyme produced by melanocytes within those tissues
Relatively little attention has been paid to regulating pigmentation via modulation of the stability of tyrosinase, which depends on tyrosinase processing and maturation in the endoplasmic reticulum (ER) and Golgi, and its degradation via the ubiquitin proteasome system (UPS) and/or the endosomal/lysosomal system

Summary

Introduction

Solar ultraviolet (UV)-B radiation (290–320 nm) is absorbed by DNA in the epidermis while UV-A radiation (320–400 nm) generates reactive oxygen species in the dermis Both types of UV radiation damage DNA directly or indirectly, which can lead to the formation of mutations, which can in turn result in UV-induced skin cancers. In the basal layer of the epidermis, there are specialized cells named melanocytes, that produce melanins. The role of those cells and the melanins is to prevent UVinduced skin cancers by absorbing the UV energy and protecting against nuclear DNA damage. Melanin synthesis in the skin, hair and eyes is regulated by tyrosinase, the critical ratelimiting enzyme produced by melanocytes within those tissues. Relatively little attention has been paid to regulating pigmentation via modulation of the stability of tyrosinase, which depends on tyrosinase processing and maturation in the ER and Golgi, and its degradation via the ubiquitin proteasome system (UPS) and/or the endosomal/lysosomal system

Role of the UPS in Melanin Synthesis

Fatty Acid-Induced Regulation of the UPS on Tyrosinase

Conclusions